Mechanisms of Human Pluripotency Transitions

The early stages of human development require precise regulation of gene regulatory networks to establish and maintain cell identities. A central transition in this process occurs when pluripotent cells shift from a nave to a formative state, enabling subsequent lineage specification. While mouse studies have uncovered many principles of pluripotency, key differences in timing and regulatory mechanisms mean that insights from rodent models cannot be directly transferred to humans. This project will systematically chart the regulatory networks that sustain nave pluripotency and drive the transition to formative pluripotency in human embryonic stem cells. Using CRISPR-based genome- wide screens, functional genomics, and single-cell transcriptomics, we will identify essential regulators and dissect their molecular mechanisms. Comparisons between mouse and human systems will further reveal species-specific features of pluripotency. By establishing robust models of human pluripotency transitions, this research will close a critical knowledge gap in developmental biology and provide a foundation for improving stem cellbased applications in disease modeling and regenerative medicine.